The goal of this project is to develop improved methods for the diagnosis and treatment of ocular inflammatory diseases (both infectious and non-infectious) in patients of all ages including uveitis, scleritis, inflammatory diseases of the ocular surface, and intraocular malignancies. The heterogeneity of primary outcome measures use in uveitic clinical trials presents practical challenges and was actively discussed this year. Over the past year clinical studies have continued to focus on examining the effectiveness of new therapeutic agents with a milder safety profile than that offered by currently available standard immunosuppressive medications. An important consideration is local therapy such as periocular injections of steroid. We showed that periocular injections were useful in reducing cystoids macular edema in a majority of patients while improving visual acuity. In general, one saw an improvement in visual acuity in one half of the patients and this occurred within 6 months. However the risk of cataract and ocular hypertension are not negligible. We continue our experience with infliximab (Remicade) and Humira, biologic agents that neutralize the biologic activity of TNF-alpha for the treatment of scleritis, and posterior segment uveitis including retinal vasculitis. Although infliximab seems to be an effective alternate therapy for the treatment of ocular inflammatory disease the potential for ocular complications may limit the usage of the agent. We evaluated the presence of T -regulatory cells in humans and defined their characteristics. We have seen that uveitis patients resistant to steroid therapy have a group of IL-17 producing cells that are steroid resistant in the CD4+CD25+ subpopulation. An ongoing protocol evaluating oral tolerance in uveitis is mentioned in a separate report. We continue to analyze vitreous cytokine levels from primary intraocular lymphoma (PIOL) and uveitic patients and continue to use the cutoff point in disease diagnosis with an IL-10 to IL-6 ratio greater than 1.0 for PIOL. We are evaluating ways to image these cells real time in the patient. As well, the MUST (multicenter uveitis steroid treatment study results showed no difference in therapeutic effect but with considerable differences in adverse effects. An extension study of MUST continues. The cost effectiveness of the fluocinolone acetonide implant versus systemic therapy was evaluated. It was found to be reasonably cost-effective when compared to systemic therapy for those patients with unilateral disease. The SITE study, in which we participated demonstrated that there was no increased mortality due to long term immunosuppressive therapy for uveitis. It has been noted that patients with a diagnosis of JIA, Behcets disease, bilateral uveitis, an history of cataract surgery, and those with a vision of 20/200 or worse are less likely to go into remission. SITE 2 has started. We have identified elevated levels of IL-17 in patients with sarcoidosis. As well, the CFH variant associated with AMD we reported to be associated with ocular sarcoidosis at the same incidence as in AMD. Family studies in African Americans with Sarcoidosis are planned. In parallel we will investigate in detail the characteristics of immunosenescence in uveitis patients.